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A gene fusion in about 1-2% of lung cancers that responds for years to targeted pills, now in their third generation.
ROS1 rearrangements (CD74-ROS1 most common) occur in ~1-2% of NSCLC, typically in younger never-smokers. Crizotinib (2016) and entrectinib (2019) were first; repotrectinib (2023) covers the G2032R solvent-front mutation; zidesamtinib (July 2026) adds TRK sparing to reduce neurologic toxicity. Also seen in cholangiocarcinoma and glioblastoma (rare).
In plain words · A gene fusion in about 1-2% of lung cancers that responds for years to targeted pills, now in their third generation.
A gene fusion in about 1-2% of lung cancers that responds for years to targeted pills, now in their third generation.
Receptor tyrosine kinase with homology to ALK; fusions constitutively activate MAPK, PI3K, and JAK-STAT.
6 products aim at ROS1: small molecules and other agents. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
PDUFA target action date stated by Nuvalent when the FDA accepted the new drug application. Nuvalent's first potential approval. Source
Tumour-specific alteration: 1 of 1 label readouts filed under it measure a sequence variant (ROS1 fusion (ROS1-positive)) absent from normal cells. HPA ROS1: RNA group enriched (epididymis 55 nTPM, lung 30 nTPM); no normal tissue stained high; highest cancer staining liver cancer (1 of 12 high). Distribution: 1 cancer family in the corpus carries a prevalence row, label threshold or catalogue link for it (Lung cancer (all types)); Open Targets associates it with 2 specific cancer types at or above 0.5 (non-small cell lung carcinoma, lung adenocarcinoma). Tissue-agnostic: Entrectinib US 2019: "ROS1-positive metastatic NSCLC; NTRK fusion solid tumours (≥12 years, extended to ≥1 month 2023)". (Rule 3 of scripts/fetch-target-specificity.ts.)
Sources: ROS1 fusion (ROS1-positive) label threshold; Human Protein Atlas ROS1 tissue; Open Targets ENSG00000047936 associations
First described 1986. Earliest sequence paper UniProt cites for the protein: Matsushime et al, Mol. Cell. Biol, 1986, "Human c-ros-1 gene homologous to the v-ros sequence of UR2 sarcoma virus encodes for a transmembrane receptorlike molecule". Source.
What a pathology or genomic report can say about this target, each with the thresholds approvals use.
Receptor tyrosine kinase with homology to ALK; fusions constitutively activate MAPK, PI3K, and JAK-STAT.
RNA: group enriched (epididymis 55 nTPM, lung 30 nTPM), detected in some normal tissues.
No normal tissue stained high.
RNA cancer enriched: Lung Adenocarcinoma 25 pTPM.
Medium only: colorectal cancer, melanoma, pancreatic cancer, skin cancer.
HPA ROS1 tissue · HPA ROS1 pathology · HPA protein class: FDA approved drug targets
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Non-small-cell lung cancer | 1-3% | Rearrangement, commonly CD74-ROS1 | cBioPortal structural variants: 25 of 915, 2.7%, in lung_msk_2017 (CD74 in 13 events, EZR in 4, SDC4 in 3, SLC34A2 in 2); 44 of 2,621, 1.7%, in nsclc_ctdx_msk_2022; 40 of 2,422, 1.7%, in luad_mskcc_2023_met_organotropism; 5 of 232, 2.2%, in lung_nci_2022. In the founding series, 18 of 1,073 screened lung cancers, 1.7%, against 31 ALK-rearranged, 2.9% (Bergethon 2012). | cBioPortal (TCGA) |
| Non-small-cell lung cancer | 1.7% | FISH, ROS1 rearrangement (18 of 1,073 NSCLC) | Bergethon 2012; enriched in younger never-smokers with adenocarcinoma | doi.org |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Crizotinib was the first ALK inhibitor, approved four years after ALK fusions were found in lung cancer; it was also the first drug for ROS1 lung cancer and for ALK-positive lymphoma and inflammatory myofibroblastic tumour in children.
Entrectinib (Rozlytrek) is a pill for NTRK-fusion cancers and ROS1 lung cancer that reaches brain metastases.
Iruplinalkib is Qilu Pharmaceutical's second-generation ALK inhibitor, approved in China in 2023 for ALK-positive non-small-cell lung cancer after crizotinib and in 2024 as first-line treatment.
The first FDA-approved gene panel that could match one biopsy to several different lung cancer drugs at once.
A ROS1 and NTRK pill that also works after other ROS1 drugs fail, with dizziness as its signature side effect.
A ROS1 lung-cancer pill approved in 2025 that works in the brain and after crizotinib, with fewer dizziness-type side effects than repotrectinib.
The current first choice for ALK-positive lung cancer in most guidelines, and the strongest evidence in solid tumour oncology that a drug can be designed to work inside the brain. Five-year follow-up has since shown the majority of patients still progression-free.
It turned the laboratory prediction into a clinical rule: after a second-generation ALK inhibitor, genotype the tumour, and treat the absence of an ALK mutation as evidence that the cancer has stopped depending on ALK.
It showed the benefit of plasma testing is not only analytical but logistical: it reaches patients who are too unwell, or whose disease is too inaccessible, for a repeat biopsy.
It is the evidence behind running plasma and tissue together at diagnosis rather than in sequence, and the 80% sensitivity figure is the reason a negative plasma result never ends the work-up.
It is the document that defines what a complete lung cancer molecular report looks like, and its asymmetry about plasma, rule in but never rule out, is the single most useful sentence in it.
It is the honest accounting of precision oncology in the disease where it works best: broad sequencing changes treatment for about one patient in three, and the bottleneck is evidence rather than detection.
It defined a class of lung cancer by a rearrangement and a clinical phenotype at the same time, and it is the reason ROS1 testing is recommended for every patient with adenocarcinoma rather than only for those with an obvious risk profile.
Query for this target: (TITLE:"ROS1" OR ABSTRACT:"ROS1") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about ROS1, not a curated reading list.
Shares Iruplinalkib, Dong-Wan Kim, LUNGevity Foundation (and GO2 for Lung Cancer), ROS1 rearrangements define a unique molecular class of lung cancers and the tags driver, kinase.
Shares Koichi Goto, Sequence: targeted therapy before immunotherapy in driver-positive NSCLC, Alexander Drilon, Clinical implications of plasma-based genotyping with the delivery of personalized therapy in metastatic non-small cell lung cancer and the tags driver, kinase.
Shares Clinical implications of plasma-based genotyping with the delivery of personalized therapy in metastatic non-small cell lung cancer, NILE: clinical utility of comprehensive cell-free DNA analysis to identify genomic biomarkers in patients with newly diagnosed metastatic non-small cell lung cancer, Oncomine Dx Target Test, Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies and the tags driver, kinase.
Shares LUNGevity Foundation (and GO2 for Lung Cancer), Sequence: targeted therapy before immunotherapy in driver-positive NSCLC, Clinical implications of plasma-based genotyping with the delivery of personalized therapy in metastatic non-small cell lung cancer, NILE: clinical utility of comprehensive cell-free DNA analysis to identify genomic biomarkers in patients with newly diagnosed metastatic non-small cell lung cancer and the tags driver, kinase.
Shares KRAS wild-type pancreatic ductal adenocarcinoma, Gene fusion, PI3K / AKT / mTOR, Receptor tyrosine kinase activation and the tags driver, kinase.
Shares PI3K / AKT / mTOR, Receptor tyrosine kinase activation, RAS / RAF / MEK / ERK (MAPK) and the tags driver, kinase.
Shares Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall, Receptor tyrosine kinase activation and the tags driver, kinase.
Shares PI3K / AKT / mTOR, Receptor tyrosine kinase activation, Non-small-cell lung cancer and the tags driver, kinase.